858. Atazanavir

Nomenclature

CAS number: 198904-31-3
(3S,8S,9S,12S)-3,12-Bis(1,1-dimethylethyl)-8-hydroxy-4,11-dioxo-9-(phenylmethyl)-6-[[4-(2-pyridinyl)phenyl]methyl]-2,5,6,10,13-pentaazatetradecanedioic acid dimethyl ester; 1-[4-(pyridin-2-yl)phenyl]-5S-2,5-bis[[N-(methoxycarbonyl)-l-tert-leucinyl]amino]-4S-hydroxy-6-phenyl-2-azahexane; BMS-232632; CGP-73547.
C38H52N6O7; mol wt 704.86.
C 64.75%, H 7.44%, N 11.92%, O 15.89%.

Description and references

Azapeptide HIV protease inhibitor. Prepn: A. Fssler et al., WO 9740029; eidem, US 5849911 (1997, 1998 both to Novartis); G. Bold et al., J. Med. Chem. 41, 3387 (1998); of bisulfate salt: J. Singh et al., WO 9936404; eidem, US 6087383 (1999, 2000 both to Bristol-Myers Squibb); Z. Xu et al., Org. Process Res. Dev. 6, 323 (2002). Comparative anti-HIV activity: B. S. Robinson et al., Antimicrob. Agents Chemother. 44, 2093 (2000). HPLC determn in plasma: E. Cateau et al., J. Pharm. Biomed. Anal. 39, 791 (2005). Clinical evaluation in HIV: I. Sanne et al., J. Acquir. Immune Defic. Syndr. 32, 18 (2003). Review of pharmacology and clinical efficacy in HIV: C. Le Tiec et al., Clin. Pharmacokinet. 44, 1035-1050 (2005); T. S. Harrison, L. J. Scott, Drugs 65, 2309-2336 (2005).

Chemical structure

Properties

Crystals from ethanol/water, mp 207-209°. [α]D 47° (c = 1 in ethanol). Insol in water (<1 μg/ml at 24°).

Derivative

Sulfate.

Nomenclature

CAS number: 229975-97-7
Reyataz (BMS).
C38H52N6O7.H2SO4; mol wt 802.93.
C 56.84%, H 6.78%, N 10.47%, O 21.92%, S 3.99%.

Properties

Crystals from ethanol + heptane, mp 195.0°, or acetone, mp 198-199° (dec). [α]D22 46.1° (c = 1 in 1:1 CH3OH/H2O, pH = 2.6). Soly in water: 4-5 mg/ml.

Therapeutic Category

Antiretroviral.

Keywords

Antiretroviral; Protease Inhibitors; HIV Protease Inhibitor